Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors

Abstract

The renin-angiotensin system has been established as an attractive target for pharmacological intervention since the discovery of first angiotensin-converting enzyme inhibitors (ACE-Is). In fact, these drugs are primarily used in the management of cardiovascular system-related diseases and renal insufficiency. Their mechanism of action involves the adjustment of balance between vasoconstrictive, hypertrophic and salt/water-retentive angiotensin II and vasodilatory and natriuretic bradykinin by the inhibition of angiotensin II biosynthesis and bradykinin degradation. Currently there are thirteen family members approved for use in humans. They differ in structure, chemistry and pharmacokinetic and pharmacodynamic properties yet they display a similar pharmacologic and toxicologic profile. All of them are effective in the treatment of hypertension as well as in cardiac insufficiency or diabetic nephropathy. Although they are generally well-tolerated several serious side-effects including life-threatening angioedema, renal failure and persistent dry cough could occur during the administration of ACE-Is, which may require the cessation of therapy. Furthermore, to provide maximum safety and efficiency of ACE-Is-based therapy, the knowledge of the related drug interactions and chronokinetics seems to be an absolute requirement. Here we discuss the above-mentioned issues regarding the pharmaceutical and chemical properties of the commercially- used ACE-Is.

Tolerability of Antihypertensive Medications in Older Adults

“…Angiotensin II also stimulates adrenal release of aldosterone, which in turn promotes sodium retention through the distal renal tubules. ARBs work through the antagonism of angiotensin II AT 1 (angiotensin II receptor subtype 1) receptors and are an option when certain adverse effects such as cough occur with the use of ACEIs [66]. Bradykinin is normally degraded by ACE; when ACEIs inhibit ACE, the half-life of bradykinin is prolonged and its concentration raised, contributing to some ADEs.…”

“…Prospective randomized study in 218 males, over 48 weeks Randomized to treatment with felodipine combined with metoprolol or irbesartan No significant difference in prevalence of ED before or after treatment in either group Felodipine-irbesartan was more beneficial to the sexual desire of hypertensive males [145] Sexual activity and function in middle-aged and older men and women with HT National Opinion Research Center sample of 4017 l community-dwelling adults, 57-85 years, of whom 75.5 % completed the interview No consistent associations between specific antihypertensive medication classes and sexual problems, suggesting the need for prospective studies [149] Risk of falls after initiation of antihypertensive drugs in the elderly Population-based self-controlled study of elderly aged 66 Several factors contribute to nonadherence to medications and resultant suboptimal control of hypertension; poor tolerability due to ADEs is only one contributory factor. Anxiety sensitivity is strongly associated with antihypertensive drug nonadherence, a situation that can be managed through the use of adaptive strategies for anxiety, with resultant better control of hypertension and lower cardiovascular risk [166].…”

Can angiotensin-converting enzyme inhibitors interfere with the free radicals? Measurement of antioxidant capacity using DPPH radical reduction examined by UV-VIS method

“…The % of inhibition increases with the improvement of antioxidant properties. The % inhibition was calculated using the formula (22): % inh. = Abs.…”

Evaluation of the combined treatment with pregabalin and inhibitors of the renin-angiotensin system against maximal electroshock in mice

“…The former comprise angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT 1 receptor antagonists used in the treatment of hypertension, heart failure and diabetic nephropathy [1,2]. Pregabalin is an antiepileptic drug (AED) used as an adjunctive treatment for focal seizures, neuropathic pain, fibromyalgia, and anxiety disorder in adult patients [3].…”